Antiplatelet Effects of Ticagrelor Versus Clopidogrel in American Indian Patients

A Single Center, Randomized, Open Label, Multiple Dose, Crossover Study of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in American Indian Patients With Stable Coronary Artery Disease

Assess the pharmacodynamic effect of ticagrelor vs. Clopidogrel in American Indian patients with stable coronary artery disease.

Study Overview

• Status: Completed
• Conditions: Coronary Artery Disease
• Intervention / Treatment: Drug: Ticagrelor; Drug: Clopidogrel

Detailed Description

A Single Center, Randomized, Open Label, Multiple Dose, Crossover Study of the Antiplatelet Effects of Ticagrelor Versus Clopidogrel in American Indian Patients With Stable Coronary Artery Disease

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • South Dakota
    • Rapid City, South Dakota, United States, 57701
      • Regional Heart Doctors/Black Hills Cardiovascular Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Documented stable CAD fulfilling any of the following, and taking 81mg ASA daily treatment:
• Females must be post menopausal for at least one year or surgically sterile for at least 6 months and negative urine pregnancy test
• Self-identified as American Indian
• Genetic Inclusion Criteria: must sign the informed consent for genetic and biological sample banking.

Exclusion Criteria:

• Any indication for oral anticoagulant or dual antiplatelet treatment
• Concomitant therapy with strong CYP3A inhibitors, CYP3A substrates with narrow therapeutic index, or strong CYP3A inducers within 14 days and during study treatment and during:
• Increased bleeding risk including:
• Diabetic patients with HbAlC > 10% at screening
• Contraindication to clopidogrel, ASA, or ticagrelor - A history of alcohol and/or substance abuse that could interfere with conduct of the trial
• Patients requiring dialysis
• Patients scheduled for revascularization (e.g., PCI, CABG) during the study period
• Any acute or chronic unstable condition in the past 30 days
• Known active or recurrent hepatic disorder
• Patients who had ACS or stent placed within 12 months of screening
• History of Uric Acid nephropathy

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Ticagrelor; Ticagrelor 180 mg loading dose followed by 90 mg bid for 7 days ± 2 days	Drug: Ticagrelor; Ticagrelor 180 mg loading dose followed by 90 mg bid for 7 days ± 2 days; Other Names: Brand Name: Brilinta; Drug: Clopidogrel; Clopidogrel 600 mg loading dose followed by 75 mg Daily for 7 days ± 2 days; Other Names: Brand Name: Plavix
Active Comparator: Clopidogrel; Clopidogrel 600 mg Loading Dose followed by 75 mg Daily for 7 days ± 2 days	Drug: Ticagrelor; Ticagrelor 180 mg loading dose followed by 90 mg bid for 7 days ± 2 days; Other Names: Brand Name: Brilinta; Drug: Clopidogrel; Clopidogrel 600 mg loading dose followed by 75 mg Daily for 7 days ± 2 days; Other Names: Brand Name: Plavix

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Compare ticagrelor's versus clopidogrel's inhibition of the P2Y12 receptor as measured by the decrease in P2Y12 Reaction Units (PRU) using VerifyNow TM.	At 2 hour time point after loading dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Compare the decrease of P2Y12 Reaction Units (PRU) by VerifyNow TM from ticagrelor and clopidogrel.		0.5 and 8 hour time points after loading dose
Compare the decrease in P2Y l2 Reaction Units (PRU) by VerifyNow™ from ticagrelor's and clopidogrel's morning dose on Day 7		At the 2, 8, and 24 hours after the last dose
To evaluate and compare the pharmacodynamic effects, measured by the vasodilator-stimulated phosphoprotein (VASP) assay (platelet reactivity index [PRI]), in all subjects		Day1: pre-dose, 0.5, 2, and 8 hours post loading dose Day 7: pre-dose, 2 and 8 hours post dose Day 8: 24 hours post final dose
Assess and to compare the percentage of subjects with High on-treatment Platelet Reactivity (HPR) at all time points after randomized study treatment.	The High on-treatment Platelet Reactivity will be defined in accordance with the following platelet inhibition level cut-off.; > 208 PRU by the VerifyNow P2Y12 assay; > 230 PRU by the VerifyNow P2Y12 assay; > 50% PRI by the VASP assay	Day 1: Pre-dose, 0.5, 2 and 8 hours post loading dose Day 7: pre-dose, 2 and 8 hours post dose Day 8: 24 hours after final dose

Other Outcome Measures

Outcome Measure	Time Frame
CYP2C19 genotyping to identifying the wild-type CYP2C19 allele (*1), and characterize common alleles known to effect the metabolism of clopidogrel (*2, *3, *4,*5,*6,*7,*8 responsible for poor metabolism and *17 allele responsible for rapid metabolism).	One time-point

Collaborators and Investigators

• Sponsor: Rapid City Regional Hospital, Inc
• Collaborators: AstraZeneca
• Investigators: Principal Investigator: James S Walder, MD, Rapid City Regional Hospital

Study record dates

Study Major Dates

• Study Start: December 1, 2012
• Primary Completion (Actual): March 1, 2014
• Study Completion (Actual): April 1, 2014

Study Registration Dates

• First Submitted: October 10, 2012
• First Submitted That Met QC Criteria: October 10, 2012
• First Posted (Estimate): October 15, 2012

Study Record Updates

• Last Update Posted (Estimate): May 5, 2015
• Last Update Submitted That Met QC Criteria: May 4, 2015
• Last Verified: May 1, 2015

More Information

Terms related to this study

• Keywords: Ticagrelor; Vascular Diseases; Cardiovascular Diseases; Coronary Artery Disease; Physiological Effects of Drugs; Platelet Aggregation Inhibitors; Clopidogrel; Pharmacologic Actions; Arteriosclerosis; Heart Diseases; Therapeutic Uses; Myocardial Ischemia; Coronary Disease; Arterial Occlusive Diseases; Hematologic Agents; Purinergic P2Y Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Purinergic P2 Receptor Antagonists
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Arteriosclerosis; Arterial Occlusive Diseases; Coronary Artery Disease; Myocardial Ischemia; Coronary Disease; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Purinergic P2 Receptor Antagonists; Purinergic Antagonists; Purinergic Agents; Ticagrelor; Clopidogrel
• Other Study ID Numbers: ISSBRIL0076